Abstract
The etiology of major neurodevelopmental disorders such as schizophrenia and autism is unclear, with evidence supporting a combination of genetic factors and environmental insults, including viral infection during pregnancy. Here we utilized a mouse model of maternal immune activation (MIA) with the viral mimic PolyI:C infection during early gestation. We investigated the transcriptional changes in the brains of mouse fetuses following MIA during the prenatal period, and evaluated the behavioral and biochemical changes in the adult brain. The results reveal an increase in RNA editing levels and dysregulation in brain development-related gene pathways in the fetal brains of MIA mice. These MIA-induced brain editing changes are not observed in adulthood, although MIA-induced behavioral deficits are observed. Taken together, our findings suggest that MIA induces transient dysregulation of RNA editing at a critical time in brain development.
Highlights
The etiology of major neurodevelopmental disorders such as schizophrenia and autism is unclear, with evidence supporting a combination of genetic factors and environmental insults, including viral infection during pregnancy
polyribocytidilic acid (PolyI):C leads to induction of the innate immune system, by activation of double-strand RNA (dsRNA) sensors, such as melanoma differentiationassociated protein 5 (MDA5) and Toll-like receptor 3 (TLR3)[18]
In order to verify that the mice we treated prenatally with PolyI:C showed major neurodevelopmental disorders (MND)-related behaviors, we conducted two behavioral experiments, the prepulse inhibition (PPI) and locomotor response to amphetamine tests
Summary
The etiology of major neurodevelopmental disorders such as schizophrenia and autism is unclear, with evidence supporting a combination of genetic factors and environmental insults, including viral infection during pregnancy. We utilized a mouse model of maternal immune activation (MIA) with the viral mimic PolyI:C infection during early gestation. The results reveal an increase in RNA editing levels and dysregulation in brain developmentrelated gene pathways in the fetal brains of MIA mice. These MIA-induced brain editing changes are not observed in adulthood, MIA-induced behavioral deficits are observed. Maternal immune activation (MIA) rodent models that are based on this observation involve exposing a pregnant rodent to specific viral pathogens, immune-stimulating agents, or proinflammatory cytokines, and evaluating the subsequent long-term brain and behavioral effects in the offspring[11]. PolyI:C leads to induction of the innate immune system, by activation of dsRNA sensors, such as melanoma differentiationassociated protein 5 (MDA5) and Toll-like receptor 3 (TLR3)[18]
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